Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta
Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta
复制标题
DOI：
10.1056/nejmoa020150
复制
发表时间：
2002-08-15
影响因子：
158.5
通讯作者：
Goldman, JM
中科院分区：
文献类型：
--
作者：
Apperley, JF;Gardembas, M;Goldman, JM
背景一小部分慢性骨髓增生性疾病患者存在血小板衍生生长因子受体β（PDGFRB）基因的组成性激活，该基因编码受体酪氨酸激酶。该基因位于染色体5 q33上，并且激活通常由与ETV 6-PDGFRB融合基因相关的t（5;12）（q33;p13）易位引起。甲磺酸伊马替尼的酪氨酸激酶抑制剂特异性抑制ABL，PDGFR和KIT激酶，并具有令人印象深刻的临床疗效在BCR-ABL阳性慢性髓细胞白血病。方法我们治疗了4例慢性骨髓增生性疾病和染色体易位涉及5 q33与甲磺酸伊马替尼（400毫克，每天）。四名患者中的三名表现出白细胞增多和嗜酸性粒细胞增多;他们的白血病细胞携带ETV 6-PDGFRB融合基因。第四例患者白细胞增多，嗜酸性粒细胞增多，和t（5;12）易位涉及PDGFRB和一个未知的合作伙伴基因，他也有广泛的提高，溃疡性皮肤病变，一直存在了很长一段时间。在皮肤病患者中，病变在治疗开始后不久就开始消退。t（5;12）易位在3例患者中在12周时检测不到，在第4例患者中在36周时检测不到。在三名携带ETV 6-PDGFRB融合基因的患者中，转录水平下降，在一名患者中，到36周时无法检测到。所有的反应是持久的，在9至12个月的follow-up.Conclusions伊马替尼甲磺酸盐诱导持久的反应与PDGFRB激活的慢性骨髓增生性疾病患者。
Background A small proportion of patients with chronic myeloproliferative diseases have constitutive activation of the gene for platelet-derived growth factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase. The gene is located on chromosome 5q33, and the activation is usually caused by a t(5;12)(q33;p13) translocation associated with an ETV6-PDGFRB fusion gene. The tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT kinases and has impressive clinical efficacy in BCR-ABL-positive chronic myeloid leukemia.Methods We treated four patients who had chronic myeloproliferative diseases and chromosomal translocations involving 5q33 with imatinib mesylate (400 mg daily). Three of the four patients presented with leukocytosis and eosinophilia; their leukemia cells carried the ETV6-PDGFRB fusion gene. The fourth patient had leukocytosis, eosinophilia, and a t(5;12) translocation involving PDGFRB and an unknown partner gene; he also had extensive raised, ulcerated skin lesions that had been present for a long time.Results In all four patients, a normal blood count was achieved within four weeks after treatment began. In the patient with skin disease, the lesions began to resolve shortly after treatment began. The t(5;12) translocation was undetectable by 12 weeks in three patients and by 36 weeks in the fourth patient. In the three patients with the ETV6-PDGFRB fusion gene, the transcript level decreased, and in one patient, it became undetectable by 36 weeks. All responses were durable at 9 to 12 months of follow-up.Conclusions Imatinib mesylate induces durable responses in patients with chronic myeloproliferative diseases associated with activation of PDGFRB.